Journal Article

Dopamine D sub(2) receptor gene polymorphisms and response to cabergoline therapy in patients with prolactin-secreting pituitary adenomas

Fustini, M F, Grottoli, S, Peri, A, Spada, A, Colao, A, Gasco, V, Borretta, G, Monte, P D, Angioni, A R, Baglioni, S, Ambrosi, B, Pigliaru, F, Barbieri, A M, Filopanti, M

2008

Overview

Dopamine-agonist cabergoline (CB) reduces prolactin (PRL) secretion and tumor size in 80% of patients with prolactin-secreting adenomas (PRL-omas) by binding type 2 dopamine receptor (DRD2). The mechanisms responsible for resistance to CB remain largely unknown. To assess the association of DRD2 with sensitivity to CB, Taql-A1/A2, Taql-B1/B2, Hphl-G/T and Ncol-C/T genotypes were determined in a cross-sectional retrospective study, including 203 patients with PRL-oma. DRD2 alleles frequencies did not differ between patients and 212 healthy subjects. Conversely, Ncol-T allele frequency was higher in resistant rather than responsive patients, considering both PRL normalization (56.6 vs 45.3%, P=0.038) and tumor shrinkage (70.4 vs 41.4%, P =0.006). Finally, [Taql A1-/Tagl B1-/Hphl T-/Ncol T-] haplotype was found in 34.5% of patients normalizing PRL with ,3mg/ week of CB vs 11.3% of resistants (P=0.021). In conclusion, resistance to CB was associated with DRD2 Ncol-T + allele, consistent with evidence suggesting that this variant may lead to reduction and instability of DRD2 mRNA or protein.